Loss of Chaotic Trabecular Structure in OPG-Deficient Juvenile Paget's Disease Patients Indicates a Chaogenic Role for OPG in Nonlinear Pattern Formation of Trabecular Bone

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Abstract

The RANK-RANKL-OPG system of osteoclast regulation may play a key role in determining chaotic structure in trabecular bone. Iliac trabecular bone from juvenile Paget's disease patients deficient in functional OPG shows parallel, anisotropic structure instead of normal chaotic structure. Evidence from experimental systems suggests that RANK-RANKL-OPG controls key nonlinear “chaogenic” parameters, such as friction, forcing frequency, feedback, and boundary forcing.

The RANK-RANKL-osteoprotegerin (OPG) system of osteoclast regulation may play a key role in determining chaotic structure in trabecular bone. Iliac trabecular bone from juvenile Paget's disease (JPD) patients deficient in functional OPG shows parallel, anisotropic structure instead of normal chaotic structure. Evidence from experimental systems suggests that RANK-RANKL-OPG controls key nonlinear “chaogenic” parameters, such as friction, forcing frequency, feedback, and boundary forcing. The Belousov-Zhabotinsky reaction-diffusion system, the catalytic oxidation of CO on platinum surfaces, and thermal diffusion in liquid helium allow visualization of nonlinear emergent patterns such as labyrinthine structures, turbulence, and cellular structures, all of which bear some resemblance to trabecular bone. In JPD, the gene for OPG (TNFRSF11B) is subject to an inactivating mutation, leading to increased resorption and accelerated remodeling. Histomorphometric images of iliac crest trabecular bone from teenagers suffering from JPD show a highly unusual array of parallel, regular trabecular plates, instead of the typical chaotic, fractal patterns of normal trabecular bone. Loss of OPG function is associated with a change from chaotic to regular structure, suggesting that the RANK-RANKL-OPG system is controlling key nonlinear “chaogenic” parameters. Looking at trabecular bone from the perspective of nonlinear pattern formation may help understand other phenomena, such as the marked dependence of trabecular bone's architectural and mechanical quality on remodeling rate independent of the trabecular bone mass.

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